Tag Archive for: stem cell therapy

Omidubicel (Expanded Cord Blood) for use in Allogeneic Transplant

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Introduction

Umbilical Cord Blood (UCB) has been used as a source of stem cells in allogeneic (donor) transplants since the late 1980s. When doing a transplant using bone marrow (BM) or peripheral blood (PB), it is necessary to have a close Human Leukocyte Antigen (HL) type match to reduce the chance of the transplant being rejected and the risk of Graft-Versus-Host Disease (GVHD). Since UCB contains more naïve cells, it does not need to match nearly as well to be used as a source of stem cells in a transplant. This is important for people who do not have good unrelated donor matches in the registries, in particular minorities who tend to be underrepresented in the registries and people of mixed race.

Since a single UCB unit contains significantly fewer stem cells than a PB or BM graft, it takes longer for a patient’s white blood (neutrophil) count and platelet count to recover when getting a UCB transplant. This is a fundamental problem of using UCB for transplants. This means that patients are at risk of infections for a longer time. There have been a number of attempts to expand the number of cells in a cord blood unit, dating back at least 20 years, but none have managed to be approved by the U.S. Food and Drug Administration (FDA).

FDA Approval

The FDA approved omidubicel to reduce time to neutrophil recovery in April, 2023. This was based on a Phase 3 randomized study (reported in Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study) that compared the outcome of patients who received omidubicel versus those who underwent conventional cord blood transplants.

Comparison of Omidubicel and standard Cord Blood transplants

The trial enrolled 125 patients who were randomly assigned to receive omidubicel (62 patients) or a standard UCB transplant (63). Patients in the standard transplant arm received a double cord transplant if the initial CB unit was not well matched or contained a smaller number of cells. 67% of those patients received a double cord transplant, 33% a single cord transplant. Three alternative myeloablative conditioning regimens were allowed and different regimens to prevent GVHD.

The time to white blood cell recovery (a neutrophils count of at least 500) and platelet recovery (a count of at least 20) was much faster in patients who received omidubicel. Patients who received omidubicel had neutrophil recovery a median of 10 days faster than patients who received a standard UCB. Platelet recovery was a median of 13 days faster for those receiving omidubicel. Patients who received omidubicel spent a median of 11 fewer days in the hospital in the first 100 days post-transplant and experienced fewer serious infections..

There are a couple of drawbacks to omidubicel. About 10% of the CB units had manufacturing or production failure. In addition, it takes about 21 days to manufacture omidubicel. These issues resulted 14% of patients not being able to receive the therapy.

Discussion

Omidubicel is a significant advance in the use of cord blood for transplants. There was a big reduction in hospital stays and infections. There may be a survival benefit with omidubicel., the study was too small to determine if there was a statistically significant increase in survival, although there seemed to be a trend toward better survival. The authors of the paper in Blood , state: “The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT”. I think this probably is an understatement and centers that use cord blood in adults and older children will rapidly start using omidubicel. No doubt there will be a high price for omidubicel, but this is likely to be balanced out by reduced number of days in the hospital.

A major question that remains unanswered is how omidubicel will now compare to transplants using an unrelated donor or a half-matched family member (haploidentical). My guess is that most centers that do not do cord blood transplants in adults will continue to use unrelated or haploidentical donors. Probably, in a few years there will be a comparison done, at least using data from transplant registries.

I asked Karen Ballen, M.D. Chief, Hematology/Oncology, University of Virginia Cancer Center for comment on omidubicel (I would also like to thank her for graciously providing comments on this article):

Omidubicel is the first product approved by the FDA for expansion of a stem cell transplant graft, in this case cord blood. The randomized clinical trial showed an advantage in neutrophil and platelet engraftment and days in the hospital. There was no survival benefit, which could potentially limit use. The cost of the product is unknown. Another drawback is the 2.5 to 3 weeks needed to manufacture. Nonetheless, this represents a major advance in the cell therapy field.

Further Reading

How Is Relapsed/Refractory DLBCL Treated?

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How Is Relapsed/Refractory DLBCL Treated? from Patient Empowerment Network on Vimeo.

What options are available if a diffuse large B-cell lymphoma (DLBCL) patient doesn’t respond to treatment or relapses? Dr. Justin Kline discusses potential next steps in treatment for DLBCL patients with relapsed or refractory disease. 

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

See More From The Pro-Active DLBCL Patient Toolkit

Related Programs:

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An Expert Defines Diffuse Large B-Cell Lymphoma (DLBCL)

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Which Emerging DLBCL Therapies Are Showing Promise?

Transcript:

Katherine:      

Let’s talk about if someone doesn’t respond to initial treatment or they relapse. Let’s start by defining some terms for the audience. What does it mean to be refractory?

Dr. Kline:       

So, refractory is a term that’s used to describe a situation where a person has received treatment but that treatment hasn’t worked as well as we have expected. And the most – probably the most important scenario is after initial treatment.

Most people, for example, who receive R-CHOP, somewhere between 80 and 85 percent will have a completely negative PET scan after treatment. That’s remission. If the PET scan is not negative and you do a biopsy and it shows that there’s still lymphoma there, that’s what’s called primary refractory. In other words, the person’s lymphoma was refractory to initial or primary treatment. And in clinical trials that are testing agents, drugs or immunotherapies in folks who’ve had multiple treatments, usually refractory is used to define someone who has either not responded or has had a very, very short response to whatever the last treatment they had was.

Katherine:                  

How does relapse then differ from refractory?

Dr. Kline:       

So, right, so relapse suggests that the lymphoma at some point was in a remission, right?

And so for example, a person gets six treatments of R-CHOP, has a PET scan at the end, the PET scan is clean. We say you’re in remission. Eight months later, the person develops a newly enlarged lymph node, and a biopsy shows that the lymphoma has come back, right? That’s what we would call a relapse. There was a period of remission, whereas refractory usually means there was never a period of remission to begin with.

Katherine:                  

Got it. How typical is it for a patient to relapse?

Dr. Kline:       

Well, again, if you look at all comers, if you treated 100 people with DLBCL, most, probably 70 to 75 percent, would go into remission. About 10 or 15 percent would have primary refractory disease and another 10 or 15 percent would have a remission that would end at some point and they would have a relapse. So, it’s not terribly common.

The problem is that once the lymphoma has either demonstrated that it’s refractory to treatment or it’s come back, it’s relapsed, it’s a little bit more difficult to cure the lymphoma at that point.

Katherine:      

How are patients treated then if they’ve relapsed or refractory?

Dr. Kline:       

Well, so for somebody who’s had primary refractory lymphoma or has a lymphoma that’s relapsed after initial therapy, again, say for the sake of argument with R-CHOP, for many, many years, the next line of treatment if you will was to administer what we call salvage chemotherapy, and this is different chemotherapy from the original R-CHOP, that’s meant to put the lymphoma back into remission. In other worse, to salvage a remission. And for folks whose lymphomas were sensitive or responded, shrunk down to that salvage chemotherapy, we would consolidate that remission.

We would make it deeper using high dose chemotherapy and an autologous or a cell, stem cell transplant. And that’s been the standard of care for younger patients for decades.

That paradigm has been challenged, particularly in refractory patients or those who have very early relapses after R-CHOP, by two important clinical trials that have demonstrated superiority of a type of immunotherapy, a cellular immunotherapy called CAR T-cell therapy, which seems to be more effective even than stem cell transplantation in that population of folks.

How Is DLBCL Treated?

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How Is Diffuse Large B-Cell Lymphoma (DLBCL) Treated? from Patient Empowerment Network on Vimeo.

Dr. Justin Kline explains what patients need to know about current DLBCL treatment, including R-CHOP, stem cell therapy, and clinical trials.

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

See More From The Pro-Active DLBCL Patient Toolkit

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 How Is DLBCL Treatment Effectiveness Monitored?

 How Is Relapsed/Refractory DLBCL Treated?

How Is Relapsed/Refractory DLBCL Treated?

Transcript:

Katherine:      

From what I understand, treatment really should start right away. So, what types of treatment are currently available to someone newly diagnosed with DLBCL?

Dr. Kline:       

Sure, so for about 20 plus years now, the standard of care for most patients with DLBCL, regardless of whether it’s a germinal center or an activated B-cell type DLBCL, is a combination of what we call chemo immunotherapy, the acronym for which is R-CHOP, and each of those letters stands for a different medication. The R stands for rituximab, which is an antibody that coats the surface of lymphomatous B cells and sort of signals the immune system to come and kill those cells.

The C is cyclophosphamide, the H is hydroxy doxorubicin, and the O is Oncovin. These are each classical chemotherapy drugs, and they each work through a different mechanism to help kill lymphoma sells. And the P is a steroid pill called prednisone, so it’s a little bit complicated, but the reason that we use cocktails of medicines to treat lymphomas is that it really works to prevent the lymphoma cells from gaining the upper hand, from developing resistance to a single type of treatment.

Katherine:      

Right.

Dr. Kline:       

Now, I should say that for certain DLBCLs, particularly those double hit lymphomas that we talked about, sometimes we use a more intensive cocktail called dose-adjusted R-EPOCH. It has largely the same medications with an additional chemotherapy called etoposide.

The difference is that R-CHOP is given – all the drugs are given intravenously, with the exception of prednisone, over a single day. The dose-adjusted R-EPOCH is given over an infusion over the course of about five days. The other point I might make is that there was a recent large clinical study that compared R-CHOP to a new regimen called polatuzumab R-CHP. So, basically the O in R-CHOP was removed and substituted for this new drug called polatuzumab vedotin, and although many, many combinations similar to R-CHOP have been compared to R-CHOP over the past 20 years and failed, this regimen, polatuzumab R-CHP in the study called the POLARIX study actually was shown to improve what we call progression-free survival by about six percent. So, it may become a new standard of care for treating DLBCL, which is exciting, because we haven’t had one in over 20 years.

Katherine:                  

Right. That’s good news.

Dr. Kline:       

Long answer to a short question, sorry about that. Yes, it is good news.

Katherine:      

That is good news. What about stem cell transplants?

Dr. Kline:       

Good question. So, for newly diagnosed patients, in this era, we rarely if ever are recommending stem cell transplant or stem cell transplantation as part of initial therapy. There are rare circumstances, but for the vast majority of patients who are, people who are diagnosed with DLBCL, it’s not recommended.

Katherine:      

Where do clinical trials fit in?

Dr. Kline:       

It’s a really good question. I practice at an academic medical center, and so one of our missions is to advance therapy and make it better. There’s no way to do that without performing clinical trials, so I think for – clinical trials aren’t for everyone. As a matter of fact, most people with lymphoma are not treated in the context of clinical trials.

But certainly I think they are important to consider, and number one, it’s possible that the particular person might be involved with the clinical trial that is very successful and actually improves their outcome. I always tell people that I see that being involved with the clinical trial is also, to some extent, an altruistic endeavor. You’re helping your doctors learn more about how to treat a type of cancer, hopefully better, maybe not, you know? So, there is some altruism that goes into clinical trials as well. So, I do think that most people who are able should consider having a second opinion. Doesn’t have to be at an academic medical center, but at least with another doctor, where clinical trial options can be discussed.